1. Technical Field
This document relates to methods and materials for using nucleic acid and amino acid sequence variants of ribonucleic acid binding motif protein 20 (RBM20). For example, this document relates to methods and materials for using nucleic acid sequence variants and/or their corresponding amino acid variants of RBM20 that are associated with dilated cardiomyopathy to identify mammals (e.g., humans) at risk of having dilated cardiomyopathy that is likely to progress to heart failure.
2. Background Information
Dilated cardiomyopathy (DCM) is a disease of the heart muscle characterized by cardiac enlargement and impaired systolic function of the heart. The more dilated the heart becomes, the less it is able to contract and pump blood from the left ventricle into the aorta. Inefficient blood pumping can lead to ankle and abdominal swelling, fatigue, shortness of breath, palpitations, and irregular heartbeat. A collection of all or a few of these symptoms is indicative of heart failure. The primary manifestation of DCM is heart failure, a major public health concern with an estimated 5.7 Americans living with heart failure and 670,000 new diagnoses each year, according to the American Heart Association. Onset of heart failure symptoms in DCM typically portends advanced myocardial disease and risk for sudden death (Desai et al., JAMA, 292:2874-9 (2006)) after years of asymptomatic progression of heart muscle weakening.
In the majority of cases of DCM, the cause is unknown, and the condition is called idiopathic DCM. Idiopathic DCM is hereditary in at least 20% of cases (Michels et al., N Eng. J. Med., 326:77-82 (1992)), suggesting genetic factors are important in its pathogenesis yet the basic mechanisms behind the pathogenicity of DCM remain largely unsolved. Familial cases of DCM provide an opportunity to discover unsuspected molecular bases, which could enable pre-clinical risk detection. In recent years, mutations in genes encoding contractile, cytoskeletal, nuclear membrane, calcium-regulating, and ion channel polypeptides have been associated with familial and sporadic DCM. Although these reports clearly establish DCM as a genetically heterogeneous disorder, the alterations in the molecular and cellular mechanisms leading to DCM as a result of these mutations remain poorly delineated.